A slew of new studies detailed at the 2015 American Thoracic Society International Conference in Denver, Colorado this week are raising concerns about e-cigarettes (electronic cigarettes, or e-cigs). While the new “drug device” studies are generally ongoing, and so unpublished, their cumulative effect was impactful.
Study One: e-cig flavorings alter lung function at cellular level
Certain flavorings—often given cute, teen-friendly names—in e-cig liquid may change key cellular functions in lungs, according to a study conducted by a team led by Temperance Rowell, a graduate student with the Cell Biology and Physiology Department of the University of North Carolina, Chapel Hill (UNC). The changes occur in cell viability, cell proliferation, and calcium signaling.
In the UNC study, cultured human airway epithelial cells were given different doses of 13 e-cig liquid flavors for 30 minutes, or 24 hours. During the 30-minute test, “Hot Cinnamon Candies,” “Banana Pudding (Southern Style),” and “Menthol Tobacco” all were toxic at high doses, and prompted a dose-dependent calcium response. The 24-hour test found those favors, in a dose-dependent fashion, impaired cell proliferation and viability.
These negative effects did not occur with nicotine or e-liquid vehicles made of propylene glycol and vegetable glycerin.
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The team is now testing the aerosolized product of e-liquid flavors on cultured primary human bronchial epithelial cells. “There could be chemical constituents present in particular flavors that we can identify via mass spectrometry that affect calcium signaling, cell viability and proliferation in airway epithelia,” the team reported in the conference abstract. “In this way, we aim to determine which chemicals in flavored e-cigarette liquids are associated with toxicity.”
Study Two: whiff of e-cig vapor reduces cough reflex sensitivity
After a single exposure to vapor from an e-cig, healthy non-smokers in a 30-participant study possessed reduced cough reflex sensitivity. The study, led by Peter Dicpinigaitis, M.D., professor of clinical medicine, Albert Einstein College of Medicine, comes on the heels of earlier work by his group, which found that chronic tobacco cigarette smokers have reduced cough reflex sensitivity. The team hypothesized the reduced sensitivity was prompted by chronic cigarette smoke-induced desensitization of airway cough receptors.
The cough reflex results in the blockage of foreign substances from the upper respiratory tract.
The 30 people in the recent study were healthy adult lifetime nonsmokers. Researchers measured cough reflex sensitivity with capsaicin, a potent red pepper extract. Subjects inhaled single breaths of ascending doubling concentrations of capsaicin until five or more coughs (C5) were elicited. The non-smokers underwent cough challenge at baseline (day 1), 15 minutes after they were exposed to an e-cigarette (day 2), and 24 hours later (day 3). Each participant’s e-cig “vaping” session involved 30 puffs of the disposable e-cigarette Blu (Lorillard Technologies). Each puff was 30 seconds apart, offering an exposure of 1.5 to 1.8 mg of nicotine, about one tobacco cigarette.
Cough reflex sensitivity was significantly diminished in subjects compared with baseline. Happily, 24 hours after the e-cig exposure, cough reflex sensitivity settled back to baseline. The mean log C5 at baseline was 0.50 ± 0.48 (SD), compared with 0.79 ± 0.62 15 minutes after e-cigarette exposure and 0.55 ± 0.53 at one day after exposure.
“The present study demonstrates that a single, acute exposure to electronic-cigarette vapor significantly diminishes cough reflex sensitivity,” wrote the team in the conference abstract. “The clinical significance, if any, of the transient, acute effect that we have demonstrated, as well as the consequences of chronic electronic cigarette exposure remain to be elucidated.”
Study Three: Lacking is evidence e-cigs work long-term
E-cigs may have been shown to significantly prevent smoking for one month compared to placebo, but there is still little evidence e-cigs work long-term, according to a study led by Riyad al-Lehebi, MBBS, of the University of Toronto Division of Respirology.
The Toronto team’s meta-analysis reviewed four studies on the efficacy and safety of e-cigarettes for promoting smoking cessation in a total of 1,011 patients. They also looked at 18 studies reporting adverse effects in 1,212 patients.
E-cigs no longer significantly affect abstinence rates at three and six month follow ups, the Toronto team found. In one study, no significant difference in six-month abstinence was observed between e-cigarettes and placebo, or between e-cigarettes and the nicotine patch.
Dry cough, throat irritation, and breathlessness were among adverse e-cig events reported in the studies. While incidence of serious adverse events did not differ between e-cigs and placebo e-cigs, e-cigs were associated with more adverse effects than the nicotine patch.
Study Four: hazardous effects of mechanical and chemical characteristics of e-cigs
E-cigs are not regulated and standardized, so they vary widely in their elements: their delivery systems, combustion apparatuses, and nicotine solutions. Thus, also varying widely may be the levels of potentially hazardous substances in their vapor, according to a study led by Daniel Sullivan, M.D., of the University of Alabama, School of Medicine. The study indeed found that differences in the mechanical and chemical makeup of e-cigs affected hazardous combustion products produced.
E-cigs tested by the team contained acrolein, an irritant linked to lung cancer risk; acetaldehyde, a potentially addictive substance also associated with an increased cancer risk; and the known carcinogen, formaldehyde. Some of the team’s tests found formaldehyde levels were comparable to those of traditional tobacco cigarettes.
The chemicals’ formation was positively correlated with the glycerol: propylene glycol ratio. Glycerol and propylene glycol are e-cigs’ nicotine solvents. The team also discovered e-cig condensate inhibited the enzymatic activity of LTA4H, an enzyme involved in lung inflammation resolution. This occurred in a dose-dependent fashion similar to that which occurs with traditional tobacco smoke.
Concluded the team in their report: “For the first time, we show that it is necessary to account for both the mechanical components of e-cigarettes, as well as the chemical makeup of their nicotine solutions, in understanding not only the generation of combustion products by these devices, but also the potential health effects of their use. Our findings also suggest that standardization of e-cigarettes, including the power and configuration of the vapor solution under study will be necessary to gain meaningful insight into potential health effects of e-cigarettes.”
Study Five: Drug Device Discovery and Development Committee award
The ATS Drug Device Discovery and Development Committee made an e-cig study by the University of California, San Diego’s Laura Crotty-Alexander one of three ATS Bear Award finalists. That study was called, “Effects of E-Cigarette Vapor on Viability, Inflammatory Responses and Antimicrobial Function of Airway Cells.”
Filed Under: Drug Discovery
